kpl-301 for subjects with giant cell arteritis

Conditions: Giant Cell Arteritis

Summary: the primary objective of the study is to evaluate the efficacy of mavrilimumab (kpl-301) versus placebo, co-administered with a 26-week corticosteroid taper, for maintaining sustained remission for 26 weeks in subjects with new onset or relapsing/refractory giant cell arteritis (gca).

this phase 2 randomized, double-blind, placebo-controlled proof of concept study will evaluate the efficacy and safety of mavrilimumab co-administered with a 26-week corticosteroid taper in subjects with gca. the study will consist of a screening period (up to 6 weeks), a 26-week double-blind placebo-controlled period during which subjects will receive blinded mavrilimumab or placebo co-administered with a 26-week corticosteroid taper, and a 12-week washout safety follow-up period during which subjects will discontinue and wash off blinded mavrilimumab or placebo.

Eligibility criteria:
selected inclusion criteria: 1. subjects with new-onset or relapsing/refractory gca. 2. westergren erythrocyte sedimentation rate \> 30 mm/hour or c-reactive protein ≥ 1 mg/ dl. 3. remission of gca at or before day 0. 4. female subjects must be postmenopausal or permanently sterile following documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or tubal ligation or having a male partner with vasectomy as affirmed by the subject, or nonpregnant, nonlactating, and if sexually active having agreed to use a highly effective method of contraception. 5. male subjects must have documented vasectomy or if sexually active must agree to use a highly effective method of contraception with their partners of childbearing potential. selected exclusion criteria: 1. transplanted organs (except corneal transplant performed more than 3 months prior to randomization). 2. concurrent enrollment in another interventional clinical study. 3. treatment with non-biologic investigational drug therapy within 4 weeks or 5 half-lives of the study agent, whichever was longer, prior to screening. 4. cell-depleting biological therapies within 12 months prior to day 0, or noncell-depleting biological therapies within 8 weeks (or 5 half-lives, whichever is longer) prior to screening. 5. treatment with alkylating agents within 12 weeks prior to screening. 6. intramuscular, intra-articular or iv corticosteroids within 4 weeks prior to screening. 7. receipt of live (attenuated) vaccine within the 4 weeks before day 0. 8. treatment with hydroxychloroquine, cyclosporine a, azathioprine, cyclophosphamide, or mycophenolate mofetil (mmf) within 4 weeks of screening. 9. female subjects who are pregnant, intending to become pregnant, or are breastfeeding. 10. known history of allergy or reaction to any component of the mavrilimumab or placebo formulation or to any other biologic therapy or prednisone or any of its excipients. 11. positive (or 2 indeterminate) quantiferon test results. 12. clinically significant active infection or infection requiring hospitalization or iv antibiotics within 12 weeks before screening or opportunistic infection within 6 months before screening. 13. chronic active hepatitis b infection. 14. subjects at a high risk of infection, a history of an infected joint prosthesis still in situ, leg ulcers, indwelling urinary catheter, or persistent or recurrent chest infections. 15. history of cancer within the last 10 years, except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured. 16. evidence of clinically-uncontrolled respiratory disease. 17. history of chronic respiratory tract infections.

Keywords: gca temporal arteritis horton's disease